Chitin and chitosan represent a family of polymers made up of N-acetyl-D-glucosamine and/or D-glucosamine subunits. Chitin can be found widely in the exoskeletons of arthropods, shells of crustaceans, and the cuticles of insects. Chitosan, although occurring in some fungi, is produced industrially by alkaline hydrolysis of chitin. At degrees of acetylation between 0% and about 60%, the upper limit depending on parameters such as processing conditions, molecular weight, and solvent characteristics, the polymer is soluble in dilute acids at a pH of above 6.3. Oftentimes the soluble form of the polymer is referred to as chitosan while for the insoluble form the term chitin is used.
Both chitosan and chitin are promising polymers for a variety of applications. Of these, biomedical applications are of particular interest because of the high biocompatibility of the two polymers, their biodegradability and their structural similarity to the glycosaminoglycans. For comprehensive reviews of potential applications of chitin and chitosan see, for example, Shigemasa and Minami, “Applications of chitin and chitosan for biomaterials”, Biotech Genetic Eng Rev 1996; 13, 383-420; Kumar, “A review of chitosan applications”, React. Funct. Polym. 2000, 46 (1), 1; and Singh and Ray, “Biomedical applications of chitin, chitosan and their derivatives”, J. Macromol. Sci. 2000, C40(1), 69.
Due to its excellent biocompatibility, chitosan has been suggested as a suitable candidate for bioabsorbable surgical sutures. The French patent application FR 2,736,552 to Houbard et al. teaches, for example, the prolongation of the bioresorption time of chitosan implants, including surgical sutures, by acetylation and de-acetylation reactions.
Typically, chitosan fibers are produced by wet-spinning techniques involving the steps of dissolving chitosan in dilute acetic acid and extruding the solution into an alkaline coagulation bath that optionally contains salts such as sodium sulfate. As an alternative method, Notin et al. in “Pseudo-dry-spinning of chitosan”, Acta Biomater. 2006, 2, 297, with reference to the international patent application WO/2005025520 describe a pseudo-dry-spinning process to produce chitosan fibers for biomedical applications, such as sutures. For comprehensive reviews on the manufacture of chitosan fibers see, for example, Rathke and Hudson, “Review of Chitin and Chitosan as Fiber and Film Formers”, J. Mater. Sci. 1994, C34, 375; Agboh and Qin, “Chitin and chitosan fibers”, Polym. Adv. Tech 1996, 8, 355; and Pillai et al., “Chitin and chitosan polymers: Chemistry, solubility and fiber formation”, Prog. Polym. Sci. 2009, 34, 641.
Fiber diameters of 0.05 millimeters (mm) or larger can be considered sufficient for the manufacture of surgical monofilament sutures, as defined by the European Pharmacopoeia 4, “Sutures, sterile synthetic absorbable monofilament”, ref. 01/2002:0666. The majority of work on chitosan fibers, however, has been focused on the wet-spinning production of chitosan staple fibers using multi-hole spinnerets. The diameter of individual chitosan filaments made by this method is typically well below 0.05 mm.
The production of chitosan monofilaments having diameters equal to or larger than 0.05 mm has been described, for example, in the above-mentioned paper by Notin et al. Using a 0.8 mm needle 2 of 22 mm length, a solution of chitosan in diluted acetic acid (or hydrochloric acid) was extruded into an ammonia atmosphere, resulting in fibers of up to 0.06 mm in diameter. While dry fibers showed a good tensile strength of up to 200 megapascal (MPa), they also exhibited remarkable swelling to between 215% and 400% of the original diameter (which corresponds to about between 450% and 1500% of the original mass) upon contact with physiological saline solution.
In “Production and characterization of chitosan fibers and 3D fiber mesh scaffolds for tissue engineering applications”, Macromol, Biosci., 2004, 4, 811, Tuzlakoglu et al. describe the manufacture of a chitosan monofilament of 0.20 mm diameter using a standard wet-spinning procedure. A solution of chitosan in aqueous acetic acid, containing minor amounts of methanol and glycerol, was extruded into a coagulation bath containing a solution of sodium hydroxide and sodium sulphate in distilled water. Dry fibers showed a good tensile strength of 205 MPa; however, fiber mass due to swelling reached 210% of the dry fiber after immersion in saline solution.
In “Coagulation rate studies of spinnable chitosan fibers”, J. Polym. Sci. A 1999, 37B, 1079, Knaul et al. have proposed a method of decreasing the swelling of chitosan fibers by applying a cross-linking reaction using glyoxal or glutaraldehyde. On the example of chitosan filaments with a diameter of 22 micrometers (μm) it was found that by using large amounts of cross-linking agent swelling could be reduced to about 135% to 150% of the original diameter (corresponding to about 180% to 220% of the original mass).